The overall objectives of the proposed research include: 1) the design, preparation, and biologic evaluation of synthetic inhibitors of the enzyme renin for the purpose of investigating whether or not a regulatory role for phosphoglyceride - phospholipase-A - lysophosphoglyceride exists in the renin-angiotensin system in vivo, and for use in studies of other physiologic processes where the renin-angiotensin system may be involved; 2) development of renin inhibitors for utilization in studies on the etiology of hypertension, on possible prognosis of surgery in patients with renal artery disease, on applications in the treatment of acute renal failure, and on the viability of kidneys for organ transplant; 3) investigation of the drug-development potential of phosphatide renin inhibitors, new structurally related derivatives, and lipo-oligopeptides in the possible medical management of certain types of hypertension in patients; 4) studies on the development and improvement of analytical methods of isolation, separation, characterization and stability of individual molecular species of phosphoglyceride and lysophosphoglyceride renin inhibitors, and structurally related physiologically active phospholipids such as anticoagulants, procoagulants, and biosynthetic precursors of prostaglandins - preparative methods would also be investigated. For chemical synthesis, conventional and innovative methods would be used. Methods of analytical and preparative separation and identification of bioactive lipids would include utilization of high pressure liquid chromatography, gas chromatography, nmr spectroscopy and mass spectrometry. Biologic evaluation of synthetic and natural product lipids would be carried out at the Cleveland Clinic in collaboration with Drs. Robert R. Smeby, Subha Sen, and F. Merlin Bumpus.